Skeletal markings show that some women who lived on the Mongolian steppe 1850 years ago appear to have been warriors, perhaps providing inspiration for the famous Ballad of Mulan

Elliott vs. Argentina is one of those court cases so important and complex that only a Power Ranger, Transformers, Legos and wooden trains can possibly do it justice. (November 30, 2012)

Cuba's artists are rising to the occasion during the coronavirus lockdown, taking to rooftops and balconies to create music or dance.

Sentient machines with empathy and morality are coming. We urgently need to make some life-and-death decisions about their rights

We are already seeing the pandemic's effects on mental health, and we need to act urgently to avoid a full-blown crisis, says Sam Howells  

Once the coronavirus pandemic is over, we must work out how to stop the spread of poor information that has helped make a bad situation that much worse

Title: Gene Mutation May Speed Alzheimer's Decline
Category: Health News
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 5/4/2017 12:00:00 AM

Title: Trump Says Obamacare Must Go as U.S. Coronavirus Cases Climb Past 1.2 Million
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Women Are Much Safer Drivers Than Men, British Study Finds
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/7/2020 12:00:00 AM

ABSTRACT

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor.

IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.

There is increasing interest in developing diagnostics that discriminate individual mutagenic mechanisms in a range of applications that include identifying population-specific mutagenesis and resolving distinct mutation signatures in cancer samples. Analyses for these applications assume that mutagenic mechanisms have a distinct relationship with neighboring bases that allows them to be distinguished. Direct support for this assumption is limited to a small number of simple cases, e.g., CpG hypermutability. We have evaluated whether the mechanistic origin of a point mutation can be resolved using only sequence context for a more complicated case. We contrasted single nucleotide variants originating from the multitude of mutagenic processes that normally operate in the mouse germline with those induced by the potent mutagen N-ethyl-N-nitrosourea (ENU). The considerable overlap in the mutation spectra of these two samples make this a challenging problem. Employing a new, robust log-linear modeling method, we demonstrate that neighboring bases contain information regarding point mutation direction that differs between the ENU-induced and spontaneous mutation variant classes. A logistic regression classifier exhibited strong performance at discriminating between the different mutation classes. Concordance between the feature set of the best classifier and information content analyses suggest our results can be generalized to other mutation classification problems. We conclude that machine learning can be used to build a practical classification tool to identify the mutation mechanism for individual genetic variants. Software implementing our approach is freely available under an open-source license.

Key Points

The translocated actin recruiting phosphoprotein (Tarp) is a multidomain type III secreted effector used by Chlamydia trachomatis. In aggregate, existing data suggest a role of this effector in initiating new infections. As new genetic tools began to emerge to study chlamydial genes in vivo, we speculated as to what degree Tarp function contributes to Chlamydia’s ability to parasitize mammalian host cells. To address this question, we generated a complete tarP deletion mutant using the fluorescence-reported allelic exchange mutagenesis (FRAEM) technique and complemented the mutant in trans with wild-type tarP or mutant tarP alleles engineered to harbor in-frame domain deletions. We provide evidence for the significant role of Tarp in C. trachomatis invasion of host cells. Complementation studies indicate that the C-terminal filamentous actin (F-actin)-binding domains are responsible for Tarp-mediated invasion efficiency. Wild-type C. trachomatis entry into HeLa cells resulted in host cell shape changes, whereas the tarP mutant did not. Finally, using a novel cis complementation approach, C. trachomatis lacking tarP demonstrated significant attenuation in a murine genital tract infection model. Together, these data provide definitive genetic evidence for the critical role of the Tarp F-actin-binding domains in host cell invasion and for the Tarp effector as a bona fide C. trachomatis virulence factor.

Pathway proteomics strategies measure protein expression changes in specific cellular processes that carry out related functions. Using targeted tandem mass tags-based sample multiplexing, hundreds of proteins can be quantified across 10 or more samples simultaneously. To facilitate these highly complex experiments, we introduce a strategy that provides complete control over...

The 78-kDa glucose-regulated protein (GRP78), an endoplasmic reticulum (ER) chaperone, is a master regulator of the ER stress. A number of studies revealed that high levels of GRP78 protein in cancer cells confer multidrug resistance (MDR) to therapeutic treatment. Therefore, drug candidate that reduces GRP78 may represent a novel approach to eliminate MDR cancer cells. Our earlier studies showed that a set of 4H-chromene derivatives induced selective cytotoxicity in MDR cancer cells. In the present study, we elucidated its selective mechanism in four MDR cancer cell lines with one lead candidate (CXL146). Cytotoxicity results confirmed the selective cytotoxicity of CXL146 toward the MDR cancer cell lines. We noted significant overexpression of GRP78 in all four MDR cell lines compared with the parental cell lines. Unexpectedly, CXL146 treatment rapidly and dose-dependently reduced GRP78 protein in MDR cancer cell lines. Using human leukemia (HL) 60/mitoxantrone (MX) 2 cell line as the model, we demonstrated that CXL146 treatment activated the unfolded protein response (UPR); as evidenced by the activation of inositol-requiring enzyme 1α, protein kinase R–like ER kinase, and activating transcription factor 6. CXL146-induced UPR activation led to a series of downstream events, including extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase activation, which contributed to CXL146-induced apoptosis. Targeted reduction in GRP78 resulted in reduced sensitivity of HL60/MX2 toward CXL146. Long-term sublethal CXL146 exposure also led to reduction in GRP78 in HL60/MX2. These data collectively support GRP78 as the target of CXL146 in MDR treatment. Interestingly, HL60/MX2 upon long-term sublethal CXL146 exposure regained sensitivity to mitoxantrone treatment. Therefore, further exploration of CXL146 as a novel therapy in treating MDR cancer cells is warranted.

Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels (i.e. ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach.

Background:

Visceral adipose tissue (VAT) may play a greater role than subcutaneous fat in increasing cancer risk but is poorly estimated in epidemiologic studies.

Mặc dù chưa có đủ tài chính để mua nhà bạn vẫn có thể sở hữu căn nhà trong mơ mà không thành con nợ dài hạn của ngân hàng với những bí kíp như: Không vay ngân hàng quá 50%, cho thuê lại chính ngôi nhà sẽ mua, tìm mọi cách tất toán trước hạn hoặc tận dụng nguồn tiền vay từ người thân...

The UK government has announced plans to police content on platforms like YouTube and Facebook, but it won't be able to do more than the social networks are already doing

Electric scooters are a nightmare. Rented by the minute, they clog up pavements and are an ungainly eyesore, but we still need them, says Donna Lu

Tech firms are making record profits but paying little tax. Now global leaders are discussing ways to make them pay their fair share

A new study found that life may be more stressful now than it was in the 1990s, especially for people between the ages of 45 and 64.

Mutations in white blood cells can contribute to abnormal immune profile after hematopoietic stem cell transplantation.

In an exclusive interview, climate activist Greta Thunberg has told New Scientist that the coronavirus pandemic shows we can act quickly in an emergency

We are already seeing the pandemic's effects on mental health, and we need to act urgently to avoid a full-blown crisis, says Sam Howells  

Once the coronavirus pandemic is over, we must work out how to stop the spread of poor information that has helped make a bad situation that much worse

Taking down the fossil fuel industry requires taking on the institutions that finance it. Even during a pandemic, this movement is gaining steam

1970 was a simpler time. (February was a simpler time too, but for a moment let’s think outside the pandemic bubble.)

Simpler because our environmental troubles could be easily seen. The air above our cities was filthy, and the water in our lakes and streams was gross. There was nothing subtle about it. In New York City, the environmental lawyer Albert Butzel described a permanently yellow horizon: “I not only saw the pollution, I wiped it off my windowsills.” Or consider the testimony of a city medical examiner: “The person who spent his life in the Adirondacks has nice pink lungs. The city dweller’s are black as coal.” You’ve probably heard of Cleveland’s Cuyahoga River catching fire, but here’s how the former New York governor Nelson Rockefeller described the Hudson south of Albany: “One great septic tank that has been rendered nearly useless for water supply, for swimming, or to support the rich fish life that once abounded there.” Everything that people say about the air and water in China and India right now was said of America’s cities then.

Follow our live coronavirus updates HERE Coronavirus: the symptoms

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Staff at an east London hospital have mounted bees onto a mural to represent every patient who has beaten coronavirus.

Pianist-singer behind “Tutti Frutti,” “Good Golly Miss Molly” and “Long Tall Sally” set the template that a generation of musicians would follow

The post Little Richard, Founding Father of Rock Who Broke Musical Barriers, Dead at 87 appeared first on My Site.

Nippon India Mutual Fund becomes the largest foreign-owned AMC in India.

Bill & Ted fans now have a chance to appear in the franchise’s next instalment.A new contest unveiled on Tuesday urges people to film themselves playing music and/or dancing to a pre-recorded demo track.

Part 6 of Tristan H. Cockcroft's nine-part expanded "Playbook" explains nine tips to use during the fantasy baseball season, from trade strategies to how to value rookies and closers.

News Corp is campaigning full-bore for the US president, with reports of a Wuhan lab ‘intelligence’ dossier being seeded across its empire

In liberal democracies, the integrity, impartiality and professionalism of intelligence agencies matters. That’s why it is essential that intelligence agencies remain aloof, not only from the political debates of the day, but also from the policy decisions that individual governments may take. The intelligence community’s core task is to provide brutally realistic analysis on the threat environments we face so that governments can then make the best-informed policy decisions possible to preserve our common security.

The failures of the intelligence community before the Iraq war, the gullibility of much of the western media, as well as the cynical manipulation of both by the political class of the day, provide us with a stark reminder of what can go radically wrong. On 8 September 2002 the New York Times published one of this century’s most consequential news articles. The front-page story, supplied by the Bush administration, claimed that Saddam Hussein had stepped up his quest for weapons of mass destruction by acquiring key components for a nuclear weapon. In the UK, the Blair government’s “dodgy dossier” compounded the error. John Howard did the same in Australia. The problem was that it just wasn’t true. These were over-egged stories designed to soften the public up for what would become a disastrous war.

Politicians have set a high bar for themselves – success on coronavirus has created community expectations that will be challenging to shift

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“Let’s not give everything back, let’s not throw away all the progress we’ve made by letting our frustration get the better of us.” This was Daniel Andrews on Friday afternoon, shortly after national cabinet resolved to gradually restart economic and social activity by July.

The Victorian premier wanted people to understand he’d be hastening slowly – the message being here in the Massachusetts of Australia, we decide how quickly we’ll remove coronavirus restrictions. We don’t apply an arbitrary national average.

A new iPhone for under £500? You'd better believe it

Lockdown life is raising new challenges for all of us, but the experience may help people empathise with single parents more, writes single mother and The Mother Edit blogger, Rebecca Cox

Today marks the start of human drug trials, as beating Covid-19 becomes a global effort. Susannah Butter reports

The COVID-19 crisis has created an unprecedented challenge for the music community, and has shed light on the sad realities faced by artists everyday. As Chair of Music Canada’s Advisory Council, I partnered with Music Canada and CONNECT Music Licensing to conduct an Artist Impact Survey. Developed in consultation with artist members of the Advisory […]

The post COVID-19 continues to hit the music industry’s most vulnerable: Music Canada survey appeared first on Music Canada.

A note to politicians: Stop blaming an entire race, creed, religion or any other social group for the actions of the radicalised. 

Australia's Lebanese Muslim Association President, Samier Dandan, said as much Tuesday when he responded to claims by Australia's own Immigration Minister Peter Dutton. 

The minister called out Lebanese Australians during parliament on Monday, responding to the wry question "Which group of people, from which country, does the minister believe should not have been allowed into Australia?"

His response was unbelievable. "The advice I have is that out of the last 33 people who have been charged with terrorist-related offences in this country, 22 of those people are from second and third generation Lebanese-Muslim background." Read more...

Crystal Palace winger Andros Townsend says the Premier League season must finish in order to maintain the integrity of the competition.

Former Charlton and Chelsea defender Paul Elliott believe there is still work to be done to eliminate racism in football, on the second National Stephen Lawrence Day.

Former Tottenham striker Dimitar Berbatov says Harry Kane must decide when it is time to leave for a "big club".

Watford join Brighton and Aston Villa in publicly disclosing opposition to neutral venue plans

FBI Director Christopher Wray said Thursday that “I have not” read special counsel Robert Mueller’s final report on Russian election...

If you think of your favourite British TV shows, one thing that stands out is the great variation in the way the actors sound. So why aren't Australians the same?